Generally, the layer by layer technique is one in which substrates including particles are coated with layers, such as alternating layers of polyelectrolytes. As described in U.S. Pat. No. 7,615,530, electrostatic layer by layer multilayer films provide a platform for immunogenic compositions for use as vaccines, for example. In an electrostatic layer by layer (LBL) multilayer film, deposition of oppositely charged polyelectrolytes onto a surface, such as a particle, provides a stable multilayer structure. Epitopes including polypeptide epitopes can be incorporated into a charged polyelectrolyte such as polypeptide, allowing for incorporation of a polypeptide epitope into the film. The films containing the epitopes can be used to elicit an immune response and provide protection against a target, such as a pathogen.
The process of electrostatic LBL fabrication is inherently repetitive. It involves coating the surface of a solid support, such as microparticles or nanoparticles, by immersion of the support in solutions of polyelectrolytes, followed by the elimination of excess soluble polyelectrolytes by a simple solvent exchange process, such as dialysis. In general, multiple immersion/elimination cycles are executed until a layer by layer film with desirable properties, for example, sufficient thickness or stability, is achieved. Many techniques can be used to execute repetitive LBL steps, but most suffer from undesirable conditions or they are difficult to automate. Automation of the LBL process is highly desirable because it replaces human actions, which are a well-known source of product variability. Additionally, if the LBL product is intended for use in humans or animals it is desirable that the process be conducted under aseptic conditions so as to avoid a terminal sterilization step that can damage the product. Accordingly, there is a need for automated tools and methods for coating particles using the LBL technique that can reproducibly and consistently produce a high quality product suitable for use in humans and animals.